The met transforming gene was isolated from a chemically-treated human osteosarcoma cell line (MNNG-HOS) using the NIH3T3 cell transfection assay. DNA prepared from the tumorigenic N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treated HOS (TE-85) cell line induces foci on NIH3T3 cells, whereas DNA prepared from the non-tumorigenic parental HOS cell line failed to induce foci. Met is unrelated to other known oncogenes or transforming genes and has been mapped to the long arm of human chromosome 7 from 7q21-7q31. The transforming activity of met is contained within 35 kb of human DNA and this region of human DNA is not rearranged within MNNG-HOS, HOS or NIH3T3 transformant DNA, nor is it amplified in MNNG-HOS cells when compared with other human cell lines. The expression of met within several human cell lines and NIH3T3 transformants has been compared, and the 5' and 3' termini of the met message within NIH3T3 transformants have been localized. Several met-related transcripts are detected in many human cell lines in culture and met expression appears to be controlled in a cell-type or tissue-specific fashion. In particular, these results show that the MNNG-HOS cell line expresses a new met RNA of 6.5 kb when compared to the non-tumorigenic HOS cell line. NIH3T3 transformants express only this aberrant RNA, which is shorter than the met RNAs of 12.0 kb, 11.0 kb, 9.5 kb and 8.0 kb detected in HOS cells. Mapping data suggest that the 6.5 kb RNA has the correct 3' end but has an altered 5' end when compared with the HOS cell RNAs. The met transforming activity, therefore, is associated with the expression of a truncated RNA product.